A role for the alpha-chain connecting peptide motif in mediating TCR-CD8 cooperation.


Autoria(s): Naeher D.; Luescher I.F.; Palmer E.
Data(s)

2002

Resumo

To generate peripheral T cells that are both self-MHC restricted and self-MHC tolerant, thymocytes are subjected to positive and negative selection. How the TCR discriminates between positive and negative selection ligands is not well understood, although there is substantial evidence that the CD4 and CD8 coreceptors play an important role in this cell fate decision. We have previously identified an evolutionarily conserved motif in the TCR, the alpha-chain connecting peptide motif (alpha-CPM), which allows the TCR to deliver positive selection signals. Thymocytes expressing alpha-CPM-deficient receptors do not undergo positive selection, whereas their negative selection is not impaired. In this work we studied the ligand binding and receptor function of alpha-CPM-deficient TCRs by generating T cell hybridomas expressing wild-type or alpha-CPM-deficient forms of the T1 TCR. This K(d)-restricted TCR is specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide(252-260) IASA-YIPSAEK(ABA)I and is therefore amenable to TCR photoaffinity labeling. The experiments presented in this work show that alpha-CPM-deficient TCRs fail to cooperate with CD8 to enhance ligand binding and functional responses.

Identificador

http://serval.unil.ch/?id=serval:BIB_C672291A6382

isbn:0022-1767

pmid:12218110

isiid:000177958200022

Idioma(s)

en

Fonte

Journal of immunology, vol. 169, no. 6, pp. 2964-2970

Palavras-Chave #Amino Acid Motifs/genetics; Amino Acid Sequence; Animals; Antigens, CD8/metabolism; Antigens, CD8/physiology; CD8-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/metabolism; Cell Line; Gene Expression Regulation/immunology; Genes, T-Cell Receptor alpha/genetics; Genes, T-Cell Receptor alpha/physiology; Humans; Hybridomas; Interleukin-2/biosynthesis; Ligands; Mice; Molecular Sequence Data; Peptide Fragments/genetics; Peptide Fragments/physiology; Protein Binding/genetics; Protein Binding/immunology; Receptors, Antigen, T-Cell, alpha-beta/biosynthesis; Receptors, Antigen, T-Cell, alpha-beta/genetics; Recombinant Fusion Proteins/biosynthesis; Recombinant Fusion Proteins/genetics
Tipo

info:eu-repo/semantics/article

article